US2004121009A1PendingUtilityA1

Method of modifying the release profile of sustained release compositions

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Assignee: ALKERMES INCPriority: Oct 17, 2002Filed: Oct 8, 2003Published: Jun 24, 2004
Est. expiryOct 17, 2022(expired)· nominal 20-yr term from priority
Inventors:James R. DaschM. Gary I. RileyPaul A. BurkeSusan A. Steitz-AbadiStephen E. Zale
A61P 43/00A61K 31/573A61K 45/06A61P 37/02A61K 9/1694A61K 9/1647A61K 9/0024
47
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Claims

Abstract

The present invention relates to a method for the sustained release in vivo of a biologically active labile agent comprising administering to a subject in need of treatment an effective amount of a sustained release composition comprising a biocompatible polymer having the biologically active labile agent incorporated therein, and a corticosteroid wherein the labile is released for a period of at least about two weeks. It is understood that the corticosteroid is present in an amount sufficient to modify the release profile of the biologically active labile agent from the sustained release composition. Pharmaceutical compositions suitable for use in the method of the invention are also disclosed.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A method for the sustained release in vivo of a biologically active labile agent comprising administering to a subject in need of treatment an effective amount of a sustained release composition comprising a biocompatible polymer having a biologically active labile agent incorporated therein wherein the labile agent is released for a period of at least about two weeks, and a corticosteroid.  
     
     
         2 . The method of  claim 1 , wherein the corticosteroid is co-incorporated into the sustained release composition.  
     
     
         3 . The method of  claim 1 , wherein the corticosteroid is separately incorporated into a second biocompatible polymer.  
     
     
         4 . The method of  claim 3 , wherein the second biocompatible polymer is the same as the biocompatible polymer of the sustained release composition.  
     
     
         5 . The method of  claim 4 , wherein the second biocompatible polymer is different from the biocompatible polymer of the sustained release composition.  
     
     
         6 . The method of  claim 1 , wherein the corticosteroid is unencapusulated but commingled with the sustained release composition.  
     
     
         7 . The method of  claim 1  wherein the corticosteroid is selected from 21-acetoxypregnenolone, alclometasone, algestone, amcinonide, beclomethasone, betamethasone, budesonide, chloroprednisone, clobetasol, clobetasone, clocortolone, cloprednol, corticosterone, cortisone, cortivazol, deflazacort, desonide, desoximetasone, dexamethasone, disflorasone, diflucortolone, difluprednate, enoxolone, fluazacort, flucloronide, flumethasone, flunisolide, flucinolone acetonide, fluocinonide, fluocortin butyl, flucortolone, fluorometholone, fluperolone acetate, fluprednidene acetate, fluprednisolone, flurandrenolide, fluticasone propionate, formocortal, halcinonide, halobetasol propionate, halometasone, halopredone acetate, hydrocortamate, hydrocortisone, loteprednol etabonate, mazipredone, medrysone, meprednisone, methylprednisolone, mometasone furoate, paramethasone, prednicarbate, prednisolone, prednisolone 25-diethylamino-acetate, prednisolone sodium phosphate, prednisone, prednival, prednylidene, rimexolone, tixocortol, triamcinolone acetonide, triamcinolone acetonide 21-oic acid methyl ester, triamcinolone benetonide, triamcinolone hexacetonide, triamcinolone diacetate, pharmaceutically acceptable mixtures thereof and salts thereof.  
     
     
         8 . The method of  claim 7 , wherein the corticosteroid is selected from triamcinolone acetonide, triamcinolone acetonide 21-oic acid methyl ester, triamcinolone benetonide, triamcinolone hexacetonide, triamcinolone diacetate, pharmaceutically acceptable mixtures thereof.  
     
     
         9 . The method of  claim 1 , wherein the labile agent is released for a period of at least about three weeks.  
     
     
         10 . The method of  claim 9 , wherein the labile agent is release for a period of at least about four weeks.  
     
     
         11 . The method of  claim 1 , wherein the biocompatible polymer is selected from poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, polycarbonates, polyesteramides, polyanydrides, poly(amino acids), polyorthoesters, poly(dioxanone)s, poly(alkylene alkylate)s, copolymers of polyethylene glycol and polyorthoester, polyurethanes, blends thereof, and copolymers thereof.  
     
     
         12 . The method of  claim 11 , wherein the biocompatible polymer is a poly(lactide-co-glycolide).  
     
     
         13 . The method of  claim 1 , wherein the sustained release composition is in the form of microparticles.  
     
     
         14 . The method of  claim 1 , wherein the biologically active labile agent is a peptide.  
     
     
         15 . The method  claim 14 , wherein the peptide is exendin-4.  
     
     
         16 . The method of  claim 1 , wherein the biologically active labile agent is a protein.  
     
     
         17 . The method of  claim 16 , wherein the protein is selected from immunoglobulins, antibodies, cytokines, interleukins, interferons, erythropoietin, nucleases, tumor necrosis factor, colony stimulating factors, insulin, enzymes, tumor suppressors, blood proteins, hormones, vaccines, antigens, blood coagulation factors and growth factors.  
     
     
         18 . The method of  claim 16 , wherein the protein is erythropoietin.  
     
     
         19 . The method of  claim 16 , wherein the protein is follicle stimulating hormone.  
     
     
         20 . The method of  claim 16 , wherein the protein is insulin.  
     
     
         21 . A pharmaceutical composition comprising a sustained release composition comprising a biocompatible polymer having an effective amount of a biologically active labile agent incorporated therein wherein the labile is released for a period of at least about two weeks and a corticosteroid.  
     
     
         22 . The pharmaceutical of  claim 21 , wherein the corticosteroid is co-incorporated into the sustained release composition.  
     
     
         23 . The pharmaceutical composition of  claim 21 , wherein the corticosteroid is separately incorporated into a second biocompatible polymer.  
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein the second biocompatible polymer is the same as the biocompatible polymer of the sustained release composition.  
     
     
         25 . The pharmaceutical composition of  claim 23 , wherein the second biocompatible polymer is different from the biocompatible polymer of the sustained release composition.  
     
     
         26 . The pharmaceutical composition of  claim 21 , wherein the corticosteroid is unencapusulated but commingled with the sustained release composition.  
     
     
         27 . The pharmaceutical composition of  claim 21 , wherein the corticosteroid is selected from 21-acetoxypregnenolone, alclometasone, algestone, amcinonide, beclomethasone, betamethasone, budesonide, chloroprednisone, clobetasol, clobetasone, clocortolone, cloprednol, corticosterone, cortisone, cortivazol, deflazacort, desonide, desoximetasone, dexamethasone, disflorasone, diflucortolone, difluprednate, enoxolone, fluazacort, flucloronide, flumethasone, flunisolide, flucinolone acetonide, fluocinonide, fluocortin butyl, flucortolone, fluorometholone, fluperolone acetate, fluprednidene acetate, fluprednisolone, flurandrenolide, fluticasone propionate, formocortal, halcinonide, halobetasol propionate, halometasone, halopredone acetate, hydrocortamate, hydrocortisone, loteprednol etabonate, mazipredone, medrysone, meprednisone, methylprednisolone, mometasone furoate, paramethasone, prednicarbate, prednisolone, prednisolone 25-diethylamino-acetate, prednisolone sodium phosphate, prednisone, prednival, prednylidene, rimexolone, tixocortol, triamcinolone acetonide, triamcinolone acetonide 21-oic acid methyl ester, triamcinolone benetonide, triamcinolone hexacetonide, triamcinolone diacetate, pharmaceutically acceptable mixtures thereof and salts thereof.  
     
     
         28 . The pharmaceutical composition of  claim 27 , wherein the corticosteroid is selected from triamcinolone acetonide, triamcinolone acetonide 21-oic acid methyl ester, triamcinolone benetonide, triamcinolone hexacetonide, triamcinolone diacetate, pharmaceutically acceptable mixtures thereof.  
     
     
         29 . The pharmaceutical composition of  claim 21 , wherein the sustained release composition has a targeted release period for the labile agent of about two weeks or more.  
     
     
         30 . The pharmaceutical composition of  claim 29 , wherein the targeted release period is about three weeks or more.  
     
     
         31 . The pharmaceutical composition of  claim 21 , wherein the biocompatible polymer is selected from poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, polycarbonates, polyesteramides, polyanydrides, poly(amino acids), polyorthoesters, poly(dioxanone)s, poly(alkylene alkylate)s, copolymers of polyethylene glycol and polyorthoester, polyurethanes, blends thereof, and copolymers thereof.  
     
     
         32 . The pharmaceutical composition of  claim 31 , wherein the biocompatible polymer is a poly(lactide-co-glycolide).  
     
     
         33 . The pharmaceutical composition of  claim 21 , wherein the sustained release composition is in the form of microparticles.  
     
     
         34 . The pharmaceutical composition of  claim 21 , wherein the biologically active labile agent is a peptide.  
     
     
         35 . The pharmaceutical composition of  claim 34 , wherein the peptide is exendin-4.  
     
     
         36 . The pharmaceutical composition of  claim 21 , wherein the biologically active labile agent is a protein.  
     
     
         37 . The pharmaceutical composition of  claim 36 , wherein the protein is selected from immunoglobulins, antibodies, cytokines, interleukins, interferons, erythropoietin, nucleases, tumor necrosis factor, colony stimulating factors, insulin, enzymes, tumor suppressors, blood proteins, hormones, vaccines, antigens, blood coagulation factors and growth factors.  
     
     
         38 . The pharmaceutical composition of  claim 36 , wherein the protein is erythropoietin.  
     
     
         39 . The pharmaceutical composition of  claim 36 , wherein the protein is follicle stimulating hormone.  
     
     
         40 . The pharmaceutical composition of  claim 36 , wherein the protein is insulin.

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